Figure 2.

Interactions between IL-35 and other immune cells in TME. IL-35 regulates the activity of immune cells in the tumor microenvironment, and is mainly produced by Bregs, DCs, NK cells, TAMs, MDSC, and N2 neutrophils. Much like the differentiation of Treg cells, IL-35 can convert Bregs to an active subset (I35-Bregs) which secrete IL-35 to promote tumor growth. With increased inhibitory receptor expression and T cell depletion, IL-35⁺ DCs can slow primary tumor growth rates, unlike other IL-35⁺ immune cells. Furthermore, IL-35 mediates diverse functions in NK cells and is obligatory for promoting the early NK cell-mediated responses to enhance primary anti-tumor immunity. TAMs, MDSCs, and N2 cells recruited by IL-35 can similarly potentiate primary tumor growth and metastatic colonization in the tumor microenvironment.